Supplementary Figure 5: Product purity and indel formation yielded by BE3 and hA3A-BE3. | Nature Biotechnology

Supplementary Figure 5: Product purity and indel formation yielded by BE3 and hA3A-BE3.

From: Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion

Supplementary Figure 5

(a) Comparison of product purity yielded by BE3 and hA3A-BE3 in genomic DNA regions with natively or induced high levels of DNA methylation. Fractions of cytosine substitutions induced by BE3 and hA3A-BE3 were individually determined at the indicated cytosines under different conditions. (b) Statistical analysis of the data in (a) showed that C-to-T fractions of base editing products induced by hA3A-BE3 was significantly higher than that by BE3 in genomic regions with high-methylation levels. n = 69 samples from three independent experiments. (c) Comparison of product purity yielded by BE3 and hA3A-BE3 in genomic DNA regions with natively or induced low levels of DNA methylation. Fractions of cytosine substitutions induced by BE3 and hA3A-BE3 were individually determined at indicated cytosines under different conditions. (d) Statistical analysis of the data in (c) showed that C-to-T fractions of base editing products induced by hA3A-BE3 was significantly higher than that by BE3 in genomic regions with low-methylation levels. n = 63 samples from three independent experiments. (e) Comparison of indel formation induced by BE3 and hA3A-BE3 in genomic DNA regions with natively or induced high levels of DNA methylation. (f) Comparison of indel formation induced by BE3 and hA3A-BE3 in genomic DNA regions with natively or induced low levels of DNA methylation. (g) Statistical analysis of the data in (a,c) showed that C-to-T fractions of base editing products induced by BE3 and hA3A-BE3 at CpG sites with high-methylation levels were significantly higher than those at CpG sites with low-methylation levels. n = 36 samples from three independent experiments. (h) Statistical analysis of normalized indel frequencies induced by BE3 and hA3A-BE3 shown in (e) and (f), setting the ones induced by BE3 as 100%. n = 39 (left panel) and 36 (right panel) samples from three independent experiments.

(b,d,g,h) P value, one-tailed Student’s t test. The median and IQR are shown.

(e,f) Means ± s.d. were from three independent experiments. Asterisks denote unusually high basal indel frequencies (or amplification, sequencing or alignment artifact) at examined VEGFA-M-a, VEGFA-M-b and VEGFA-M-c sites in NT.

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